42.6: Introduction to Nuclear Reprogramming
Nuclear reprogramming is the process of switching gene expression of one cell type to that of another cell type, usually from a differentiated cell state to an undifferentiated cell state. Differentiation occurs during processes such as development and morphogenesis, tissue regeneration, and malignancy. Cells can also be artificially induced to reprogram their gene expression by techniques such as nuclear transfer, induced pluripotency, and cell fusion. Such techniques have many applications in the fields of molecular medicine, biotechnology, and oncology.
A Brief History
In 1952, Briggs and King transplanted a nucleus from a frog blastula into an enucleated frog egg. The resulting embryo developed into a normal tadpole, demonstrating nuclear reprogramming. A few years later, Gurdon and colleagues performed a similar experiment using the nuclei of intestinal epithelia from adult frogs. Despite the nucleus being fully differentiated and specialized, the transplanted eggs developed into swimming tadpoles. This experiment led to the first use of the word "clone" in reference to animals.
Dolly - The First Clone
Dolly was the first animal cloned from an adult somatic cell. Nuclei from the mammary gland cells of an adult sheep were harvested and transferred to an enucleated sheep ovum in a procedure called somatic cell nuclear transfer (SCNT). The egg was then transplanted into a female sheep, who carried it to term and gave birth to Dolly. This successful cloning spawned attempts to clone other mammals. Examples of successfully cloned mammals include deer, pigs, and horses.
Serial Nuclear Transplant
One of the major applications of nuclear reprogramming is the production of pluripotent stem cells. The first round of nuclear transplant from differentiated somatic cells into enucleated eggs produces fully viable pluripotent stem cells in scarce proportions. Most embryos from transplanted eggs are not fully reprogrammed; however, grafting these cells into normal embryos increases the proportion of reprogrammed cells. Thus serial nuclear transplantation is a more efficient method of obtaining pluripotent stem cells.